TY - JOUR A2 - Kleinjan, Alex AU - Carrière, Virginie AU - Arshad, Muhammad Imran AU - Le Seyec, Jacques AU - Lefevre, Benjamin AU - Farooq, Muhammad AU - Jan, Aurélien AU - Manuel, Christelle AU - Touami-Bernard, Laurence AU - Lucas-Clerc, Catherine AU - Genet, Valentine AU - Gascan, Hugues AU - Girard, Jean-Philippe AU - Chalmel, Frédéric AU - Lamontagne, Lucie AU - Piquet-Pellorce, Claire AU - Samson, Michel PY - 2017 DA - 2017/05/21 TI - Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis SP - 1359064 VL - 2017 AB - The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver. SN - 0962-9351 UR - https://doi.org/10.1155/2017/1359064 DO - 10.1155/2017/1359064 JF - Mediators of Inflammation PB - Hindawi KW - ER -